PHSL 3051 renal physiology

function of the kidneys

1. regulation of water, inorganic ion balance, acid base balance

2. removal of metabolic waste products from the blood and their excretion in the urine

3. removal of foreign chemicals from the blood and their excretion in the urine

4. gluconeogenesis

5. production of hormones/enzymes

primary organs of the urinary system

1. kidney

2. ureter

3. bladder

4. urethra

layers of the kidney

renal cortex = outer layer

• contains renal corpuscles, convoluted tubules, cortical nephrons

renal medulla = inner layer

• contains renal pyramids, long loops of henele, collecting ducts

the nephron

the functional unit of the kidney

the nephron tubules

1. bowmans capsule (part of corpuscle)

2. proximal convulated/straight tubule

3. loop of henele

4. distal convulated tubule

5. collecting duct

the nephron blood supply

1. a renal artery

2. afferent arteriole

3. glomerular capillaries

4. efferent arteriole

5. peritubular capillaries (possibly vasa recta, if in medulla)

6. a renal vein

portal system

an arrangement by which blood collected from one set of capillaries passes through a large vessel or vessels, to another set of capillaries before returning to the systemic circulation

the renal corpuscle = 

glomerular capillaries + bowmans capsule

nephron =

glomerular (renal) corpuscle + renal tubule

segments of the nephron

two types of nephrons

1. cortical (85%)

2. juxtamedullary (15%)

cortical nephron

• short or no loops of henele

• do not contribute to hypertonic medullary interstitium

• change in volume and consumption of filtrate

juxtamedullary nephron

• long loops of henele

• generate gradient in medulla important for H2O reabsorption

• peritubular capillaries are called the vasa rectua

• concentrate the filtrate

juxtaglomerular apparatus (JGA) composition

1. juxtaglomerular cell patch (afferent arteriole)

   1. senses pressure and releases renin when it is low

2. macula densa cell patch (distal convoluted tubule)

   1. senses flow (specifically Na+ and Cl- and sends paracrine signals to afferent arterioles)

sympathetic nerve from CVCC

1. constricts afferent arteriole

2. causes renin secretion from juxtaglomerular cells (special secretory cells)

renin

an enzyme/hormone that is important for blood pressure regulation

basic renal processes

1. glomerular filtration

   1. 20% of plasma is filtered, 80% continues into peritubular capillaries

2. tubular secretion

   1. from 80% that wasnt filtered

3. tubular reabsorption

   1. reabsorbs from filtrate and put back into plasma *prevents excretion in urine

processes for X

1. freely filtered

2. 100% secreted

processes for Y

1. freely filtered

2. partially reabsorbed

processes for Z

1. freely filtered 

2. 100% reabsorbed *more excreted in urine

1. glomerular filtration

• 20% of plasma is filtered, 80% continues into peritubular capillaries

• plasma proteins and cells are too big for filtration

• negatively charged membranes, also exclude plasma proteins

• filtrate = blood plasma except for RBC and proteins

  • glomerular filtrate is plasma without cells or plasma proteins

• useful molecules like nutrients are reabsorbed, while waste products and toxins are secreted

• **GFR = 125 mL/min (180 L/day)

3 layers of GFR

1. capillary endothelium (50x more leaky than other typical capillary bed)

2. basement membrane (negative charge)

3. bowmans epithelium (i.e. podocytes

filtered load vs excreted load (3 important equations)

1. FL = GFR x [P]

FL = flow/min GFR = mL/min P = mg/mL

2. EL = V x [U]

EL = mg/min V= urine flow rate, mL/min U = mg/mL

3. if EL < FL, net reabsorption

4. if FL < EL, net secretion

starling forces in glomerular filtration

favoring filtration

• glomerular capillary blood pressure (PGC) → 60 mmHg

opposing filtration

• fluid pressure in bowmans space (PBS) → 15 mmHg

• osmotic force due to protein in plasma (πGC) → 29 mmHg

Net glomerular filtration pressure = PGC - PBS - πGC → 16 mmHg

renal arterioles regulate PGC and thus GFR

2. tubular reabsorption

• filtered loads are HUGE (180 L/day of water)

• reabsorption of water, ions, nutrients, etc. is almost complete

• reabsorption of wastes is incomplete → excreted

modes and routes of tubular reabsorption

99% of filtrate volume is reabsorbed 

*tight junctions vary by region

1. diffusion

   1. lipid soluble substances that dont need carriers

2. meditated transport

   1. large/charged substances (glucose)

transcellular route

1. luminal membrane

2. basolateral membrane

3. renal interstitial fluid

4. peritubular capillaries

paracellular route

1. through tight functions

2. renal interstitial fluid

3. peritubular capillaries

substances needing protein carriers have a transport maximum (Tm)

example: glucose

• glucose is freely filtered, and in health, is fully reabsorbed in the proximal tubule - the plasma glucose of a healthy person almost never becomes high enough to cause glucose excretion in the urine

• however, in uncontrolled diabetes mellitus, plasma glucose concentration may rise high enough to cause the filtered load of glucose to exceed the transport max, resulting in urinary glucose excretion

renal sodium regulation

Notes

• when plasma volume drops, a decrease in GFR reduces Na+ and H2O loss

• regulation of sodium reabsorption

  • renin/angiotensis/aldosterone system

renal sodium regulation steps

renal sodium regulation ANP

atrial natriuretic peptide

• “the anti-aldosterone”

renal water regulation

there is also a baroreceptor reflex for
vasopressin/ADH secretion

• although this reflex plays a lesser role under most physiological circumstances compared to the
  osmoreceptor reflex

renal water regulation

tubular secretion

• foreign chemicals and toxins

  • penicillin

• usually involves active transport

  • coupled to Na+ reabsorption

  • i.e. secondary active transport

• most secretion occurs into the proximal tubules

  • except K+ and H+ ions are mainly secreted into the distal tubule

• secreted substances can have a Tm too

renal plasma clearance definition/equation

the volume of PLASMA per unit time from which all of a substance is removed/cleared by the kidneys and excreted in the urine

renal plasma clearance

• RPC measurements can be used to determine how well the kidneys are functioning or how a substance is handled by the kidney

  • very important when figuring out dosing, developing new drugs, etc. 

• inulin (an exogenous substance) is freely filtered but not secreted or reabsorbed

• RPCinulin = GFR (typically 125 mL/min)

• RPC of any new substance will show how that substance is handled by the kidneys

renal plasma clearance outcomes

RPC > GFR, substance is NET secreted

RPC < GFR, substance is NET reabsorbed (or partially filtered)

RBCinulin = GFR

renal plasma clearance of creatinine

a more practical, less invasive way of determining GFR

• produced by muscles at a constant rate (byproduct of normal skeletal muscle metabolism)

• freely filtered

• not reabsorbed

• slightly secreted

• RPCcr = to true GFR

renal plasma flow definition/equation

• the volume of plasma going to the kidneys per minute

• PAH is freely filtered and essentially 100% secreted

• normal RPF is 625 mL/min

renal plasma flow

micturition (urination)

the micturition reflex is a single complete cycle of…

1. progressive and rapid increase of pressure

2. a period of sustained pressure

3. return of the pressure to the basal tone of the bladder

• once a micturition reflex has occurred but has not succeeded in emptying the bladder, the nervous elements of this reflex usually remain in an inhibited state for a few minutes to an hour or more before another micturition reflex occurs

• as the bladder becomes more and more filled, micturition reflexes occur more and more often and more powerfully

Na+ reabsorption in the proximal tubule

65% of reabsorption occurs here and is non regulated

Na+ reabsorption in the distal tubule and cortical collecting duct (distal nephron)

Na+ reabsorption occurring here is regulated by hormones, no Tm

• ex. aldosterone builds Na+ channels and Na+/K+ ATPases

distal tubule/collecting duct

there are diuretics that block the actions of aldosterone, and thus inhibit the reabsorption of Na+ from the distal tubule/collecting duct

water follows Na+ passively by osmosis (2 routes)

1. paracellular

   1. main water route in proximal tubule (leaky tight junctions)

   2. non regulated

2. transcellular

   1. main water route in the distal tubule and collecting ducts (very tight junctions)

   2. requires the insertion of aquaphorins (regulated by ADH/vasopressin)

review: Na+ and H2O reabsorption (proximal tubule/loop of henle)

• Na+ reabsorption is high and constant (not regulated)

• H2O permeability is high and constant (not regulated)

• reabsorption of Na+ and H2O are coupled

review: Na+ and H2O reabsorption (distal tubule/collecting duct)

• Na+ reabsorption is variable, is regulated by aldosterone, and is NOT directly coupled to water reabsorption

• water permeability is variable, regulated by ADH, and requires the renal medullary gradient

the renal medullary gradient

the countercurrent multiplier system

1. active transport of NaCl (reabsorption) from the ascending limb

2. ascending limb is impermeable to water

3. water reabsorption via osmosis from the descending limb

4. recycling of urea from the collecting duct

concentration of urine

• because of the hyperosmotic medullar ISF, filtrate can become highly concentrated with a low volume in the presence of ADH

• net result: excretion of a low volume of highly concentrated urine

concentration of urine requires ADH

aquaporins 3 and 4 (AQP3, AQP4) are always present in the basolateral membrane. AQP2 is the only present on the luminal membrane if ADH is present

summary: importance of each nephron region

the response to sweating

• sweat comes out of your ECF and contains both water and NaCl

• both must be preserved after severe sweating in order to maintain blood volume and osmolarity

thirst and salt appetite

• kidneys can excrete excess water and Na+ that you ingest but can only reduce the rate (cant completely stop excretion) at which you lose them in times when you dont eat/drink enough

  • you must urinate some volume, so there will be fluid loss even when you are dehydrated

• you need regular intake to replace regular losses, and need to intake extra when excess fluid is lost through regular processes like sweating, vomiting, diarrhea, hemorrhage

thist

thirst must be obeyed, but keep in mind…

• caffeine dilates afferent arterioles

• alchohol inhibits ADH secretion

respiratory vs metabolic acid base disorders